1,2-dihydroisoquinoline → 1,2,3,4-Tetrahydroisoquinoline

Participants

Reaction Conditions

Reaction Steps

Dichloro-(p-cymene)ruthenium (II) dimer (0.20 mmol) is added to a solution of N-((1R,2R)-2-amino-1,2-diphenyl-ethyl)-2,4,6-trimethylbenzene-sulfonamide (0.40 mmol) and triethylamine (0.80 mmol) in acetonitrile (3.0 mL). The mixture is stirred for 1 h at 80° C. and added to a solution of the respective dihydroisoquinoline (28.0 mmol) in dichloromethane (30 mL). An azeotropic mixture of formic acid and triethylamine (5:2, 14 mL) is added (gas evolution). After 90 min a sat. aqueous NaHCO3 solution (200 mL) is added to the dark red solution. The layers are separated, the aqueous layer is extracted twice with DCM (2×200 mL) and the combined organic extracts are concentrated in vacuo. The residue is dissolved in isopropanol (1600 mL) and treated with a solution of HCl in isopropanol (5-6 M, 10 mL). The obtained hydrochloride salt is recrystallized to give the respective 1,2,3,4-tetrahydroisoquinoline with high enantiomeric excess as determined by chiral HPLC. The hydrochloride salt is converted to the free base by extraction with sat. NaHCO3 solution/dichloromethane. The absolute configuration of the respective product is assigned in analogy to the literature (N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 4916-4917).

Provenance & Evidence